4&#39;(beta-ethyl)-morpholine ester of nicotinic acid and its production



Patented Mar. 28, 1950 4( {3-ETHY L) MORPHOLINE ESTER OF NICO- TINICACID AND ITS PRODUCTION Hans Sutfi, Schaffhausen, Switzerland, assignorto Gila; Limited, Schaffhausen, Switzerland No Drawing. ApplicationAugust 31, 1946, Serial No. 694,432. In Switzerland September 15,1945

6 Claims. 1

The subject matter of the invention is a process for theproduction ofthe 4' -(c-ethyl) -morpholine ester of pyridine-3-carboxy1ic acid, whichhas been found to be a valuable therapeutic substance, more particularlyone possessing, inter alia, good spasmolytic properties which isespecially efiicacious for suppressing neurogenio spasms. The process ischaracterised by the feature that a compound selected from the groupconsisting of nicotinic acid, its anhydride, a nicotinyl halide, anester of nicotinic acid, or a salt of nicotinic acid, for example analkali salt thereof, is caused to act upon 4-(p-hydroxyethyl)-morpholine or 4- (p-halogen-ethyl) -morpholine.

The invention also covers the new 4W5- ethyl) -morpholine ester ofpyridihe-Ii-carboxylic acid for the treatment of spasms.

Example 1 A mixture of 20 gins. of nicotinic acid and 21.3 gms. of4-(c-hydmxy-ethyl)-morpholine in 100 gms. of xylene is heated at itsboiling point, so that water formed in the reaction distils off slowly.As soon as 2.9 gms. of water have collected in the receiver, theremaining xylene is distilled off in vacuo. The oily residue, whichconsists of the 4'-(p-ethyl) -morpholine ester of pyridine- 3-carboxylicacid, is purified by distillation in a good vacuum. Yield: 29.1 gms,corresponding to 82% of the theoretical. The product of the process is acolourless liquid which boils at 192 to 194 C. at a pressure of 17 mms.and is very soluble in water, methanol and ethanol.

Example 2 To a suspension of 14.6 gms. of sodium nicotinate in 200 c. c.of absolute ethanol are added 15.0 gms. of 4-(p-chlor-ethyl)-morpholine. The mixture "is heated for 4 hours on the water bath undera reflux condenser, sodium chloride separating out slowly. The cooledreaction mixture is freed fro the sodium chloride by filtration and thealcohol is distilled off. An oily residue remains which is purified bydistillation under a good vacuum. Yield: 21.1 gms. of the 4'-( 3- ethyl)-morpholine ester of pyridine-3-carboxylic acid, corresponding to 89.2%of the theoretical. The product of the process is a colourless liquidwhich boils at 192 to 194 C. at a pressure of 1'7 mms. and is verysoluble in water, methanol and ethanol.

What I claim is:

1. A process for the production of the 4'-(pethyl) morpholine ester ofpyridine-3-carboxylic acid by reacting a compound selected from thegroup consisting of nicotinic acid esters and salts of nicotinic acid,with a compound selected from the group consisting of 4-(8-hydroxyethyl) morpholine and 4 (,3 halogenethyl) -morpholine.

2. A process for the production of the 4'-(pethyD-morpholine ester ofpyridine-3-carboxylic acid, comprising reacting nicotinic acid with 4-(c-hydroxy-ethyl) -morpho1ine.

3. A process for the production of the 4'-(,3- ethyl) -morpholine esterof pyridine-3-carboxylic acid, comprising reacting an alkali salt ofpyridine-3-carboxylic acid with a 4-(p-halogenethyl) -morpholine.

4. A process for the production of the 4'-(pethyl) -morpholine ester ofpyridine-S-carboxylic acid, comprising reacting an alkali salt ofpyridine-3-carboxylic acid with 4-(fi-chlor-ethyD- morpholine.

5. The 4-(,8-ethyl) -morpholine ester of pyridine-3-carboxylic acid.

6. A process for the production of 4'-(p-ethyl) morpholine ester ofpyridine-3-carboxylic acid which comprises heating a mixture ofnicotinic acid, 4 8 hydroxy-ethyl) morpholine and xylene and distillingon the water formed in the reaction.

HANS SUTER.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Name Date 1,421,604 Steffens July 4, 19222,425,723 Blicke Aug. 19, 1947 2,430,116 Holmes, et a1 Nov. 4, 1947OTHER REFERENCES J. A. C. S.,vo1. 53 (1931), pp. 2763-2769.

Blicke et al., J. Am. Chem. Soc., 64, 1721-1724 (1942), Jour. OrganicChem. (Jan., 1945) PD. 26-28.

Sidgwick, Organic Chemistry of Nitrogen, page 522..

1. A PROCESS FOR THE PRODUCTION OF THE 4''-(BETHYL) - MORPHOLINE ESTEROF PYRIDINE-3-CARBOXYLIC ACID BY REACTING A COMPOUND SELECTED FROM THEGROUP CONSISTING OF NICTINIC ACID ESTERS AND SALTS OF NICOTINIC ACID,WITH A COMPOUND SELECTED FROM THE GROUP CONSISTING OF4-B-HYDROXYETHYL) - MORPHOLINE AND 4 - (B - HALOGENETHYL) - MORPHOLINE.